Anaesthesia for intestinal short circuiting in the morbidly obese with reference to the pathophysiology of gross obesity. Sixteen extremely obese patients were anaesthetized for intestinal short circuiting operations. Severe obesity may cause pathological cardio-pulmonary changes. Cardiovascular alterations include increased systemic, pulmonary artery and pulmonary capillary venous pressure. Cardiac output, total blood volume and left ventricular work increase. Expiratory reserve volume and consequently functional residual capacity decrease with gross obesity. Functional residual capacity falls below closing volume and inspired gas may be distributed to non-dependent lung zones, resulting in decreased ventilation/perfusion ratios and arterial hypoxaemia. Low total respiratory compliance increases the oxygen cost of the work of breathing. Obesity may change the dose requirements for regional anaesthesia and long-acting muscle relaxants. General anaesthesia may also reduce functional residual capacity. We used a technique of anaesthesia which consisted of epidural analgesia with intra-operative mechanical ventilation and which specifically avoided volatile inhalation agents and long-acting muscle relaxants. All patients were extubated immediately after operation and returned to the recovery room for an average duration of 26 hours. Post-operative treatment included humidified oxygen, chest physiotherapy and elevation of the head of the bed to 45 degrees. Each patient's respiratory progress was monitored by repeated determinations of arterial blood gases and vital capacity and by serial chest X-rays. None of the patients in this group required post-operative tracheal intubation and mechanical ventilation.


Ultrastructural evidence of the hepatotoxic effect of halothane in rats following in-utero exposure. Eight pregnant Sprague-Dawley rates were exposed to 10 ppm halothane 8 hours/day and 5 days/week throughout pregnancy. Liver samples were obtained from the pups for electron microscopy. Degenerative changes such as myelin-figure formation, focal-cytoplasmic degradation; fatty changes and cellular necrosis were observed. Leukocytic infiltration and phagocytosis of the cellular debris by Kupffer cells were also evident. The present investigation has demonstrated the hepatotoxic effects of halothane on the foetal liver. The role of halothane as an occupational hazard is considered.


The cardiovascular effects of ketamine in hypotensive states. Ketamine was found to raise the systemic arterial blood pressure but not necessarily the perfusion in hypovolaemic states. However, in hypotensive states of short duration from endotoxin treatment, it improved the haemodynamics with increase in both the perfusion and the systemic pressure. The implications of these observations for clinical situations were discussed.


Coagulation-fibrinolysis system in man during Ethrane anaesthesia and surgery. The coagulation-fibrinolysis system was studied during Ethrane anaesthesia and gynaecological operations in 20 patients. No particular change was noted in the platelet counts, which remained within the normal range. In the coagulation system, no appreciable change was observed except for the partial thromboplastin time (P.T.T.) which was significantly short-ended, both 30 minutes after the start of operation and in the recovery room when the patient had completely awakened from the anaesthesia. In the fibrinolytic system, the plasminogen level and the fibrinogen level declined significantly. It is considered that the fibrinolytic system is prominently accelerated under Ethrane anaesthesia, but the haemostatic mechanism works in such a manner that bleeding is controlled. However, Ethrane anaesthesia should be avoided or pre-operative administration of an antiplasmic agent recommended for patients with an abnormal haemostatic mechanism.


Central nervous system effects of bupivacaine. The central nervous system and concurrent cardiovascular effects of bupivacaine infusion were studied in cats. It was possible to block cortical E.E.G. desynchronization resulting from a sensory stimulus with bupivacaine. The earliest subcortical change that occurred was rhythmic activity in the amygdala and later in the hippocampus. Occasionally, this activity appeared simultaneously in both these sites. Diazepam pretreatment raised the seizure threshold of bupivacaine. Diazepam was also effective in terminating established seizure activity resulting from bupivacaine. All animals pretreated with diazepam (Valium) or diazepam solvent developed cardiac dysrhythmias durind bupivacaine infusion. The possible clinical significance of the interaction of bupivacaine and diazepam solvent is considered.


[Conservation of the blood].

[Conservation of the blood]. Many factors already contribute to limit the amount of bank blood available for therapeutic use; a possible reduction in the amount of available blood could stem from the relative indifference of young people towards the gift of blood and the increase in the size of the pool of positive carriers of Australian antigen. Moreover, new operations appear (coronary by-pass) which increase the demand for blood. It is imperative that we adopt attitudes and practice techniques that will contribute to the conservation of blood. This paper discusses the advantages of an active blood bank committee which, alone, can reduce the consumption of blood by 20 percent. Moreover, actual techniques for conservation of blood are reviewed: controlled hypotension, haemodilution and intraoperative blood salvage.


Measurement of intratracheal oxygen concentrations during face mask administration of oxygen: a modification for improved control. Direct measurement of the inspired tracheal oxygen concentration was made in patients breathing through standard aerosol face masks. Factors affecting the tracheal FIO2 were analyzed using both mechanical and mathematical models. When oxygen is delivered to the face mask at low flow rates, there is considerable patient variation in the measured tracheal FIO2. Delivery of oxygen at higher flow rates (15 litres per minute or greater), reduces such variation. Furthermore, turbulent air currents within and around the face mask reduce the measured FIO2 and contribute to fluctuations in the FIO2. This effect may be virtually eliminated by placing shields around the mask orifices as described. Using the shielded mask, it is possible to deliver the desired oxygen concentration to the patient more accurately and to maintain humidification of the delivered gases. Changes desired in inspired oxygen concentration are accomplished by changing the concentration of the incoming gas mixture, and not by merely changing the flow rate of oxygen delivered to the system. Using the shielded mask, it is possible to deliver an inspired oxygen concentration of 100 per cent. This is not true with most other commonly used face masks, and, therefore, caution should be used to avoid administration of unnecessary high inspired oxygen concentrations with this type of mask.


A method for measuring oxygen consumption and cardiac output in intensive care units. A simplified measurement of oxygen consumption was investigated in 15 spontaneously ventilating and 11 apnoeic patients in the intensive care unit following open-heart surgery, using a Godart Pulmonet type 11e. Three consecutive measurements were performed on each patient to define the reproducibility of the method. The coefficient of variation of VO2 was plus or minus 3.16 per cent and plus or minus 3.42 per cent in spontaneously breathing and apnoeic patients respectively. Arterio-mixed venous oxygen difference (CaO2-CVO2) was also measured and cardiac output (CO) calculated using the Fick principle, in the spontaneously ventilating patients. Coefficient of variation of CaO2-CVO2 and CO values were plus or minus 4.63 per cent and plus or minus 4.70 per cent respectively.


Glycopyrrolate methobromide: 2. comparison with atropine sulphate in anaesthesia. A double blind study of 98 patients was undertaken to compare the clinical usefulness of atropine and glycopyrrolate for pre-anaesthetic medication and their relative effectiveness in antagonizing the muscarinic effects of neostigmine methylsulphate given to reverse neuromuscular blockade. Intramuscular administration of atropine 0.4 mg or of glycopyrrolate 0.2 mg produced the same degree of dryness of the pharynx. However, glycopyrrolate was found to be a more potent antagonizer of the increased salivation induced by neostigmine. By intramuscular administration, both drugs produced the same degree of tachycardia, although atropine tended to cause no change in the pulse rate or even to produce bradycardia in a greater number of patients. Administered intravenously, atropine produced a more significant tachycardia in a large number of patients prior to neostigmine administration, although the protection against a decreased pulse rate from neostigmine is greater in those patients who received glycopyrrolate. It would appear, therefore, that glycopyrrolate is more effective in antagonizing the muscarinic effects of neostigmine methylsulphate.


Effect on isoflurane anaesthesia and surgery on thyroid function in man. The effect of isoflurane (Forane) anaesthesia and surgery on thyroid function was investigated in nine male patients. Isoflurane anaesthesia alone for 30 minutes prior to the start of surgery increased plasma triiodothyronine uptake (T3U) and thyroxine (T4) level by 18 and 20 per cent, respectively. Free thyroxine index (FTI) values in blood increased by 62 per cent during the same period. One hour of surgical procedure further elevated these parameters. Our data indicate that isoflurane anaesthesia and surgery increase circulating thyroxine in man.


Response to hypercapnia under ketamine anaesthesia. The respiratory response to hypercapnia in dogs anaesthetized with ketamine was increased. This respiratory stimulation was most probably due to a direct effect of the drug on the medullary respiratory neurones. This effect was not modified by preanaesthetic medication pentobarbitone 5 mg/kg or morphine 0.1 mg/kg. Catecholamine response to hypercapnia was essentially the same as that reported by hypercapnic dogs anaesthetized with thiopentone.


Cell-free protein synthesis in t,e rabbit liver ribosomal system. II. Large scale preparation of purified 80S ribosomes. A procedure for the preparation of a large quantity of biologically active, highly purified ribosomes from rabbit liver is described. The method employs polyethylene glycol-dextran sulfate parition and DEAE-cellulose chromatography to overcome the limitations encountered in conventional procedures. The entire process takes only 48 h to obtain 10,000 A(260) units of ribosomes. The ribosomes thus obtained are predominantly 78S particles with a constant protein-RNA ratio of 0.95. The ribosomes are free from RNase, amino-acyl-tRNA synthetase, and amino-acyl-tRNA: protein transferase activity. The protein synthesizing activity is dependent on added mRNA and protein factors. These ribosomes are stable for prolonged periods of storage in a liquid nitrogen refrigerator.


Distribution of newly formed fatty acids among glycerolipids of isolated perfused rat liver. Livers of chow fed rats were perfused 1-3 h with buffer, glucose, albumin, and red blood cells, made up in 100 percent D(2)O. Glycerolipids were isolated and the deuterated fatty acids determined by gas chromatography with mass spectrometry on Silar 5 CP. Percentage of replacement by deuterated acids ranged from 1 to 14, of which palmitate was 87 percent. Differences were found in total lipid class and in subcellular distribution of the newly synthesized acids. Microsomes had 37 percent more deuterated acids than the total or floating fat. At 3 h the highest replacement was found in diacylglycerols (17 percent) and free fatty acids (11 percent). Of the palmitate in hepatic choline and ethanolamine phosphatides, 6.9 percent and 4.7 percent, respectively, contained dueterium. The serine and inositol phosphatides had a higher proportion of deuterated palmitate (7.7 percent) than other phosphatides. The data support the hypothesis that palmitate is incorporated into glycerolipids largely via de novo synthesis while stearate enters them by deacylation-acyl transfer replacement.


Distribution of newly formed palmitate and stearate among molecular species of choline and ethanolamine phosphatides. The choline and ethanolamine phosphatides derived from isolated rat livers during perfusion with 75 percent deuterated water (Kuksis, A., Myher, J.J., Marai L., Yeung, S.K.F., Steiman, I. & Mookerjea, S. (1975) Can. J. Biochem. 53, 509-518) were resolved into molecular species by argentation thin-layer chromatography. The time course of percentage replacement of the newly synthesized fatty acids in each molecular species was determined by gas chromatography with mass spectrometry. The results confirmed the earlier postulated differential utilization of palmitic and stearic acids in glycerolipid biosynthesis as well as supported the hypothesis of a precursor-product relationship between the oligoenoic and tetranoic species of both phosphatides. Calculations of half-lives gave values of 14-19 h for palmitoyl oligoenes, 40-50 h for palmitoyl tetraenes, and 22-28 h for palmitoyl hexaenes of both choline and ethanolamine phosphatides. The corresponding stearoyl species had half-lives which ranged from 89 to 200 h. Evidence was obtained for a metabolic heterogeneity among subsets of molecular species recognized on the basis of combinations of new and old glycerol and fatty acids in the same glycerolipid molecule.


Characterization of malate dehydrogenase isozymes in wheat germ. Malate dehydrogenase of wheat germ exists in multiple molecular forms (isozymes). Comparisons of some physical properties such as Stoke's radii, sedimentation constants, electrophoretic mobilities on polyacrylamide gel, chromatographic behaviors on DEAE-cellulose, stabilities to heat and iodacetamide inactivation, as well as kinetic parameters were described. When all these properties are considered together, at least five isozymes were found to associate with cytoplasm, mitochondria, glyoxysomes and proplastids of wheat germ. Wheat germ malate dehydrogenases are specific for the reduction of oxaloacetate and its monoesters. At least one carboxylic group of oxaloacetate must be free, in order to exhibit substrate activity, and maximum binding of oxaloacetate is achieved when both carboxylic groups are free. Soluble malate dehydrogenase and organelle-associated malate dehydrogenase can be differentiated readily in that the former can not utilize 4-ethyl oxaloaceode of ATP inhibition.


Carboxylesterases (EC 3.1.1). Purification and titration of chicken, sheep, and horse liver carboxylesterases. Chicken, sheep, and horse liver carboxylesterases have been purified by procedures involving ammonium sulfate fractionation, ion-exchange chromatography and gel filtration on Sephadex. The actual yields of the procedures described were as follows: chicken, 1 g from 2 kg of liver powder (chloroform-acetone); sheep, 200 mg from 400 g of powder (chloroform-acetone); horse, 230 mg from 800 g of powder (acetone). The purified enzymes are free of non-carboxyl-esterase protein as shown by gel electrophoresis, although they do contain electrophoretic variants. The equivalent weight of the chicken enzyme is 67,000 based on titration with p-nitrophenyl diethyl phosphate or bis(p-nitrophenyl) phosphate, whereas those of the sheep and horse enzymes are similar to 69,500 and similar to 70,000, respectively, based on titration with p-nitrophenyl dimethylcarbamate.


Identification of ornithine and arginine conjugates of cholic acid by mass spectrometry. Nalpha-Cholylornithine, -arginine, and -histidine were prepared according to a method previously employed for the chemical synthesis of the monoamino acid conjugates of bile acids. The products were shown to involve the alpha amino group of the dibasic amino acids by examination of the mass spectra of the original compounds, their lactams, their methyl esters and the methyl ester acetates. Only the methyl ester acetates gave detectable amounts of molecular ion. The free acids and the methyl esters of Nalpha-cholylornithine and -arginine gave identical lactams upon sublimation from the direct insertion probe. The synthetic Nalpha-cholylarginine was shown to yield a mass spectrum identical to that of an arginocholic acid recovered from the bile of an isolated perfused rat liver.


A radio-gas chromatographic method for determining the specific radioactivity of glycolic acid in -14C-labeled leaf tissue. A method for the extraction and quantitative determination of both the mass and radioactivity of glycolic acid from -14C-labeled leaf tissue is described. The recoveries of both mass and radioactivity from standard [1-14C]glycolic acid solutions averaged 98 percent, and recovery of radioactivity added to plant samples as [1-14C]glycolic acid was over 90 percent after the complete procedure. The method was reliable with total samples containing as little as 130 nmol of glycolic acid. The mass of glycolic acid recovered from sunflower leaf tissue was proportional to the amount of tissue extracted. In experiments with different plant material, the amount of glycolic acid varied between 530 and 1120 nmol/dm-2 of leaf tissue. The specific radioactivity of the glycolic acid in sunflower leaf tissue during photosynthesis in -14CO(2) was never more than 20 percent of the specific radioactivity of the -14CO(2) supplied.


Membrane protein synthesis in Micrococcus lysodeikticus and selective effect of chloramphenicol. Micrococcus lysodeikticus cytoplasmic membranes labeled with ]-14C]arginine plus [-14C]-threonine were prepared and subjected to mild washing treatments to fractionate membrane proteins. Polyacrylamide gel electrophoresis of total membranes, in the presence of sodium dodecyl sulfate, results in the separation of 28-30 bands of labeled protein. Three peaks of protein show higher specific radioactivity than the others. Chloramphenicol at 100 mug/ml inhibits the incorporation of labeled precursors into membrane proteins by 45-70 percent, some of them being more affected by the antibiotic. From all available results, we suggest that the partial inhibitory effect shown by this antibiotic could be due to the existence of specific biosynthetic sites for some membrane proteins, which are differently affected by chloramphenicol.


Thiocyanate ion formation in rapeseed meals. Meal prepared from unheated rapeseed (Brassica napus cv. Zephyr) showed the presence of t,iocyanate ion, while meal from heated seed of the same cultivar did not show detectable amounts. Unheated seed meal on autolysis, and heated seed meal on incubation with thioglucosidase, yielded increased amounts of thiocyanate ion. Various commercial rapeseed meals showed the presence of t,iocyanate ion only after enzyme incubation. Low glucosinolate, cv. Bronowski, and higher glucosinolate, cv. Zephyr on enzymic incubation yielded comparable amounts of thiocyanate ion, suggesting that the precursor responsible in the two varieties was the same and present in similar quantities. No formation of thiocyanate ion was observed on incubation of sinigrin with thioglucosidase. Rats dosed with heated meal, containing intact glucosinolate, showed a slight increase of thiocyanate ion in the urine as compared with control rats dosed with water, while a relatively large increase followed dosing with sinigrin. Rats dosed with meal containing free thiocyanate ion excreted the ingested thiocyanate ion almost quantitatively.


The effect of temperature on the rate of conversion of p,p-DDT to p,p-DDE in brook trout (Salvelinus fontinalis). Brook trout (Salvelinus fontinalis) were maintained in flowing fresh water at 2, 10, and 18 degrees C and injected intramuscularly with p,p-[-14C]DDT. Fish were killed at intervals up to 16 weeks after injection, and analyzed by a combination of thin-layer chromatography, gas-liquid chromatography, and liquid-scintillation counting. Only one labelled metabolite, p,p-DDE, was detected during the experimental period. Its rate of production varied with temperature; after 16 weeks, about 9, 13, and 19 percent of the original p,p-DDT in fish maintained at 2, 10, and 18 degrees C, respectively, had been converted.


Citrate transport in guinea pig heart mitochondria. Guinea pig heart mitochondria loaded with [-14C]citrate show exchanges of radioactivity at 30 degrees C with added citrate, L-malate and phosphoenolpyruvate. These exchanges are inhibited by benzene-1,2,3-tricarboxylate. Measurements of rates of citrate transport indicate that the activity of this transporting system is low in heart mitochondria compared to that observed in liver mitochondria. The K(m) values obtained indicate a similarity to those obtained in liver. Citrate oxidation by coupled mitochondria was also found to be slow at 30 degrees C but was inhibited by benzene-1,2,3-tricarboxylate. The role of mitochondrial citrate transport in control of glycolytic flux in the heart is discussed.


Titration study of guaiacol oxidation by horseradish peroxidase. Titration of guaiacol by hydrogen peroxide in the presence of a catalytic amount of horseradish peroxidase shows that the reduction of hydrogen peroxide proceeds by the abstraction of two electrons from a guaiacol molecule. In the same way, it can be demonstrated that 0.5 mol of guaiacol can reduce, at low temperature, 1 mol of peroxidase compound I to compound II. Moreover, the reaction between equal amounts of compound I and guaiacol at low temperature produces the native enzyme. A reaction scheme is proposed which postulates that two electrons are transferred from guaiacol to compound I giving ferriperoxidase and oxidized guaiacol with the intermediary formation of compound II. The direct two-electron transfer from guaiacol to compound I without a dismutation of product free radicals must be considered as an exception to the general mechanism involving a single-electron transfer.


An incubation medium for the elevation of adenosine triphosphate and 2,3-diphosphoglycerate in fresh and long-preserved human erythrocytes. The levels of adenosine triphosphate (ATP) and 2,3-diphosphoglycerate in freshly drawn human erythrocytes can be tripled by a 2 h incubation at 37 degrees C in a medium containing 21 mM glucose, 1.8 mM adenine, 5 mM pyruvate, 10 mM inosine, and 96 mM phosphate. Similar incubation conditions will restore the levels of ATP and 2,3-diphosphoglycerate in erythrocytes from blood levels preserved for 12 and 15 weeks, respectively, to those of fresh cells. Omission of pyruvate from the incubation medium further increases the level of ATP slightly, but there is little elevation of 2,3-diphosphoglycerate. Under these conditions labelled pyruvate and lactate production from [14-C]glucose or [14-C]inosine is not diminished, but labelled fructose 1,6-diphosphate, rather than 2,3-diphosphoglycerate, accumulates. In addition, omission of pyruvate from the incubation medium, with a concomitant decrease in accumulation of 2,3-diphosphoglycerate, diminishes the concentration of inorganic phosphate required for optimal ATP elevation. A 5 h incubation in the glucose-adenine-pyruvate-inosine-phosphate medium elevates the levels of ATP and 2,3-diphosphoglycerate in erythrocytes from blood preserved in the cold for 15 weeks to twice that of fresh cells, indicating that the cells retain their metabolic potential even after prolonged storage at 2 degrees C. The medium may provide a method of rejuvenating 10-12 week cold-preserved erythrocytes for transfusion purposes, by a  1 h incubation at 37 degrees C.


Isolation and partial characterization of a sulfogalactoglycerolipid from rat brain. The brain of adult rats were analyzed for the presence of 35-SO4-containing glycolipids following intraventricular injection of Na2-35SO4. Radiochromatographic analyses revealed the presence of two minor 35-SO4-containing glycolipids, in addition to sulfogalactosylceramide. One of these two minor sulfolipids was isolated and tentatively identified as a 1-O--alkyl-2-0-acyl-3-(3'-sulfogalactosyl)-glycerol, a compound recently demonstrated to be the major glycolipid of mammalian testis. The alkyl and acyl compositions of the compound from rat brain are more heterogeneous than those from rat testis. The non-sulfated form of the galactoglycerolipid was also detected in rat brain. The amount of the sulfogalactoglycerolipid in rat brain is 0.19 mumol per gram wet weight, approximately one-third of the amount in rat testis (per gram wet weight), and is approximately one-fifteenth that of sulfogalactosylceramide in rat brain. The possible significance of the common occurrence in brain and testis of sulfated and non-sulfated galactolipids is discussed.


Phosphatidylethanolamine in liver mitochondria and endoplasmic reticulum: molecular species distribution and turnover. Phosphatidylethanolamine from mitochondria and microsomes of guinea pig liver was separated by thin-layer chromatography into eight different classes differing in degree of unsaturation. The fatty acid compositions and molar proportions of each class isolated from microsomes were very similar to the corresponding class in mitochondria. In both organelles about half of the total was dienoic species while tetraenes comprised approximately 20%. Stearic acid was the major saturated fatty acid and in each membrane a greater selectivity for stearate over palmitate was found in each sub-class of phosphatidylcholine. Following the intraperitoneal injection of [2 minus-3 H]glycerol, the labelling of each molecular class of phosphatidylethanolamine showed very similar progressions in microsomes and mitochondria over a 3 h interval. In both organelles the highest relative specific activity was attained by penta-plus hexaenoic classes, while the large dienoic class had the lowest relative activity, which, however, increased with time. Analysis of the dienoic class of phosphatidyl-ethanolamine from whole liver showed it to be constituted by a rapidly turning over palmitoyl-linoleoyl fraction and a slowly labelled stearoyl-linoleoyl fraction, a pattern also exhibited by dienoic phosphatidylcholines. The similarities in profile of molecular classes of phosphatidylethanolamine and in the kinetics of labelling in vivo point to a close metabolic relation between the lipids of both organelles, suggestive of a transfer of different molecular classes at comparable rates from the endoplasmic reticulum, the site of synthesis, to the mitochondria. This is consistent with numerous other studies in vitro that have demonstrated inter-organelle exchange of lipids.


Glutamic-pyruvic transaminase activity related to red blood cell age. Red blood cell glutamic-pyruvic transaminase (GPT) phenotypes and catalytic activities were studied in normal subjects and in patients with various hemolytic syndromes associated with reticulocytosis. To assess the effect of cell age of GPT activity, young cells were separated from older cells by centrifugation, and the catalytic activities were compared. In normal blood, there was a progressive fall in GPT activity from the top layer (younger cells) to the bottom layer (older cells), with a mean ratio of 1.90 plus or minus 0.42. Similarly, in the blood of patients with reticulocytosis, the enzyme activity of the reticulocyte-rich layer was higher than that of the layer containing older cells (mean ratio 1.94 plus or minus 0.95).


Anesthesia of bulls undergoing surgical manipulation of the vas deferentia. Twelve bulls ranging from 341 to 545 kilograms in body mass were successfully anesthetized for either vasectomy or prosthetic vas deferens implantation with a combination of thiopental sodium, glyceryl guaiacolate, nitrous oxide, halothane and oxygen. Duration of anesthetic administration was 119.2 plus or minus 24.2 (S.D.) minutes. Righting reflexes returned 15.0 plus or minus 8.0 minutes after cessation of anesthetic administration and the bulls were capable of standing within 46.6 plus or minus 17.8 minutes. Interpretations of pulse rate, respiratory rate and eye reflexes were related to anesthetic depth and maintenance. A control mean respiratory frequency of 28.8 plus or minus 3.6 per minute compared to minimum and maximum frequencies of 26.8 plus or minus 5.1 and 37.6 plus or minus 6.3, respectively, during anesthetic maintenance. A control mean pulse frequency of 91.6 plus or minus 15.9 per minute compared to minimum and maximum frequencies of 84.8 plus or minus 13 and 102.3 plus or minus 13.4, respectively, during maintenance of anesthesia. Methods for avoiding complications related to anesthetic induction, maintenance and emergence were described. Specific pharmacological aspects of atropine, halothane and nitrous oxide were emphasized in light of their application to ruminant anesthesia.


Suppression of the pathogenic effects of Strongylus edentatus larvae with thiabendazole. Four pony foals were inoculated with Strongylus edentatus infective larvae and on days 3 and 4 postinfection two of the ponies were treated with thiabendazole, each at the rate of 440 mg/kg of body weight. Total circulating eosinophil counts in untreated ponies increased to over 1700 per cu mm after the second week postinfection. In the treated ponies as well as in an uninfected untreated pony eosinophil counts did not increase beyond 100 per cu mm. At necropsy on day 35 postinfection the cecum, colon and omentum of treated ponies were normal and few tracks were present on the surface of the liver. In untreated ponies nodules were observed on the serosal surface of the cecum and right ventral colon and white foci and tracks were numerous on the surface of the liver. A total of 53 fourth stage larvac was recovered from the livers of the thiabendazole treated ponies and 1194 from the untreated ones.


Coagulation and fibrinolysis in the dog. A range of tests of coagulation and fibrinolysis was measured in "normal" dogs and compared with values obtained in "normal" humans by the same methods. The hematocrit platelet count, fibrinogen and plasminogen were similar in dogs and in humans. The prothrombin and partial thromboplastin times were considerably shorter in the dog than in man but the thrombin clotting time was comparable. Fibrinolysis was more active in dogs but the levels of fibrin degradation products were low, suggesting that there was no significant fibrin deposition and lysis occurring in vivo.


An evaluation of low temperature sterilization of trichinae infected park. Twenty-four refrigeration trials at temperatures ranging from minus 13 degrees C to minus 195.8 degrees C were carried out on trichinous porcine meat samples ranging in size from 120 gm to 11 kg. The findings reaffirmed that Canadian regulations regarding refrigeration treatment of pork and pork products to destroy trichinae are satisfactory. Results also demonstrated the presence of a critical temperature about minus 30 degrees C below which trichinae in meat do not survive for any appreciable period of time.


The kinetics of hematopoiesis in the light horse II. The hematological response to hemorrhagic anemia. Hemorrhagic anemia was experimentally produced in three Standardbred horses by removing approximately 63% of the red cell mass and the accompanying plasma during a three  day interval. Red cell parameters were examined daily for 45 days and then weekly until termination of the experiment 250 days after production of the anemia. Leukocytes, platelets and bone marrow aspirates were examined at regular intervals for 25 days after the final phlebotomy. At 24 hours after the last bleeding, 75-selenomethionine was injected intravenously to measure the lifespan of the newly produced erythrocytes. The erythrocyte lifespan was found to be 139 days as compared to the 155 day erythrocyte lifespan for three normal standardbred horses measured previously by similar techniques. The maximum decrease in erythrocyte numbers occurred four, two and two days following the last phlebotomy to 43, 39 and 44% of the original values. The prebleeding erythrocyte levels were regained at approximately 63, 91 and 98 days respectively. During the initial 45 days post phlebotomy the maximum increase in mean cell colume was 2, 4 and 7 mj-3 respectively. During the recovery period there was erythrocyte production of 6.84, 6.99, and 6.12 x 10-9 cells/kg/day. At the same time the absolute production of hemoglobin was 44.6, 50.0, and 51.0/gm/day or on a relative basis 0.096, 0.114 and 0.113 gm/kg/day.


The kinetics of hematopoiesis in the light horse III. The hematological response to hemolytic anemia. The hematological response to acetylphenylhydrazine hemolytic anemia was studied in three standardbred horses. The lifespan of erythrocytes produced during the most severe phase of the anemia were measured with 75-selenomethionine and found to be 144 days as compared to the 139 day lifespan in response to hemorrhagic anemia or 155 days in normal standardbred horses measured previously using the same technique. The erythrocyte counts returned to initial values in 42 days (37, 34 and 54 days) a mean erythrocyte production of 6.4 times 10-12 erythrocytes/day. The mean hemoglobin production was 0.31 gm/kg body weight/day as compared to 0.11 gm Hb/kg/day previously observed in response to hemorrhagic anemia. The mean increase in erythrocyte mean cell volume was 12 mu-3 during the acute response phase to hemolytic anemia in contrast to the absence of a significant increase in the mean cell volume as previously observed during response to hemorrhagic anemia. Free Heinz bodies separated from erythrocytes during the acute phase could not be differentiated from platelets on the hemocytometer counting chamber with standard techniques.


A simple method for rapid identification of Sphaerophorus necrophorus isolates. A hemagglutination inhibition test for the rapid identification of Sphaerophorus necrophorus is described. Erythrocytes from six species of animals were tested and human cells were found to be the best agglutination indicators. Antiserum prepared in rabbits was found to be specific for S. necrophorus hemagglutinins when tested against 20 isolates of S. necrophorus and 117 other bacteria belonging to 22 genera. The possibility of using a hemagglutination inhibition test for the detection of bovine necrobacillosis was explored.


The development of Ascaris suum in calves. To determine the development of Ascaris suum after a primary and a secondary infection, 18 calves were inoculated with 2,000,000 infective eggs and examined from 18 hours to 13 days postinfection. At 18 hours larvae were recovered from the wall of the abomasum, duodenum and jejunum. They were found in small intestine lymph nodes on the third day, in the liver at five days and were most abundant in the lungs on days 7 and 9. The pattern of recovery of larvae from the lung between days 5 and 13 postinfection was similar after a primary or a secondary infection. Slower growth of larvae following a secondary infection was the only evidence of resistance to A. suum. There were no pathological changes observed in the alimentary canal. White foci were found on the surface of the liver as early as the third day. The rapid decline in the number of A. suum in the lungs after the ninth day was considered to be related to immobilization or death of larvae soon after the reaction to them commences.


Combined therapy in the management of laryngeal carcinoma. The subject of combined therapy for carcinoma of the head and neck is as perplexing now as it was in its beginning. Low vs high dose pre-operative radiation for carcinoma of the larynx remains a valid question. A total of 92 patients with advanced laryngeal carcinoma were studied at the University of Illinois. The results of treatment for  2 patients receiving planned low dose pre-operative radiation and 30 patients receiving planned high dose pre-operative radiation have been studied, using the actuarial method to calculate survival. Improved survival and decreased complications are evident in the low dose pre-operative group as compared to the high dose pre-operative group.


Intermediate dose pre-operative radiotherapy for cancer of the larynx. - End results. A retrospective study has been made of the role of intermediate (4500-5000 rads in five weeks) pre-operative radiotherapy in the treatment of advanced carcinoma of the larynx. The results of treatment in 72 cases treated at the University of Virginia have been analyzed with particular attention to local recurrences and complications. The local recurrence rate is comparable to that achieved with higher doses of pre-operative irradiation and the complication rate and the pre-operative level of radiation dose employed. Deaths from causes other than local recurrence indicate that a considerable number of patients die from a second primary or distant metastases even though the local disease has been controlled.


Combined pre-operative irradiation and surgery for advanced cancer of the larynx and laryngopharynx. (A 14 year correlative statistical and histopathological study). A carefully planned clinical program of combined pre-operative radiation and surgery has been conducted by the Department of Otolaryngology at The Mount Sinai Hospital for 14 years in an effort to improve the survival rate for advanced cancer of the larynx and laryngopharynx. An extensive histopathological study of resected larynges and radical neck specimens was undertaken in 1961 in order to determine the effects of pre-operative radiation. A very careful statistical analysis has been made of the survival experience of this series of cases. The three and five year survival rates have been computed by the actuarial method. The histopathological study entailed a serial section study of 26 larynges and 21 radical neck dissection specimens. These studies have been most informative as to the nature of the radiobiologic process involved in the destruction of laryngeal cancer. In addition, the study has been revealing as to the ability of radiation to sterilize cancer in the neck specimens. The clinical correlate of this histologic finding has been the observation of reduced cervical recurrences in patients treated with combined therapy. In conclusion, our statistics seem to indicate that our combined therapy method has improved the survival rates of patients with advanced cancer of the larynx and laryngopharynx.


Verrucous carcinoma of the larynx. - A study of its pathologic anatomy. In the 10 years between 1964 and 1974, 276 patients with infiltrating carcinoma of the larynx included 31 cases of varrucous carcinoma (11 per cent of the series). This tumor is characterized by the pushing invasion of well differentiated squamous epithelium growing in a vertically folded invasive pattern. The tumor appears most frequently in the two decades between 50 and 69 years of age. The ratio of male to female patients was 3.4:1. Verrucous carcinoma has a predilection for the supraglottic regions of the larynx. Cut surface of the tumor shows clefting and sharp margins. Lymph node metastasis occurred in five cases. The marked inflammatory host reaction can cause misleading cervical lymphadenopathy. Problems in diagnosis are discussed.


Spindle cell carcinoma of the larynx.

Spindle cell carcinoma of the larynx. A clinicopathologic correlation of 39 cases of a histologically biphasic malignant neoplasm of the larynx is presented. The histologic pattern of this entity was mainly that of a malignant spindle cell process, but a definite squamous cell carcinoma component was evident. Grossly the tumors were usually prominently polypoid. A morphologic transition of the squamous cell carcinomatous element into the spindle cell component was strongly suggested, supporting the contention that this entity is pathogenetically a pleomorphic or spindle cell squamous cell carcinoma. Follow-up information on 20 cases indicated a two-year mortality of 40 per cent, refuting the contention that this entity is of low-grade malignancy. Complete surgical removal of the neoplasm, with or without irradiation, offered the best therapeutic approach. Irradiation alone was unsuccessful.


Paradoxical nasal obstruction.

Paradoxical nasal obstruction. The phenomenon of paradoxical nasal obstruction is described. An understanding of this phenomenon is made possible by the knowledge of the nasal cycle and of the concept of total nasal airway resistance. These topics are reviewed and two patients with paradoxical nasal obstruction are described. Direct observation, rhinomanometric tests and serial tomograms were utilized to substantiate these findings.


Intramuscular hemangioma in the head and neck. Intramuscular hemangioma is a distinct type of hemangioma occurring within skeletal muscle and making up less than one per cent of all hemangiomas. They occur most often in the trunk and extremities, perhaps beacuse of the larger muscle volume in thos areas. 13.5 per cent of intramuscular hemangiomas do occur in the head and neck region and for this reason they should be considered in the differential diagnosis of head and neck masses. The first case of an intramuscular hemangioma of the digastric muscle is presented and confirmed by electron microscopic sections. An interesting finding in this tumor is the proliferation of both endothelial cells and pericytes. Hemangiomas are classified according to vessel size; "large vessel" cavernous, "small vessel" capillary, and "mixed". Various etiologies and modalities of treatment are discussed, and total excision with ligation of the feeding vessels is advocated to prevent the high incidence of later recurrence.


Gentamicin - Progressive cochlear toxicity. Four patients with severe thermal burns showed Gentamicin cochlear toxicity. The hearing loss ranged from moderate to severe and was progressive in the three patients that were followed. These side effects were seen even with only topical application of Gentamicin to large surface burns of the body. All patients had an associated loss of bestibular function. None of the patients during treatment with Gentamicin was in renal failure. These finding are discussed in the light of current knowledge of Gentamicin toxicity, blood levels, and absorption from surface burns of the body.


Prognostic value of nerve excitability test in Bell's palsy. This paper reports the experience of the authors using facial nerve excitability test in Bell's palsy as a tool to understand better the prognosis in that pathology. The authors made a retrospective study of 222 cases of Bell's palsy, followed by serial facial nerve excitability test. The goal of this study as to define correlations between facial nerve excitability test (N.E.T.) values, the rate and degree of recovery OF PATIENTS PRESENTING A Bell's palsy. Results indicated that incomplete paralysis with a normal N.E.T. forecasts a fast and complete recovery in less than three months. Complete paralysis with a normal N.E.T. also forecasts a complete recovery. Those cases of complete paralysis with an abnormally elevated (greater than 2 m. amp.) N.E.T. lead to unsatisfactory results in 27.7 per cent of patients and of these 66.6 per cent took more than three months to recover if at all. Of the patients with complete paralysis and no response to facial nerve stimulation, 73 per cent showed an unsatisfactory recovery.


[Abnormalities of recovery of the facial nerve]. This paper presents 235 cases of facial palsy. These cases are part of a group of 455 cases and they were chosen because their clinical study and evolution were well documented. Abnormalities of facial nerve recovery are described and the importance of each one with reference to the group is determined. Two cases of particular interest are described, and comments are offered on the incidence of abnormality of recovery according to the type of lesion and to the importance of the electrical dysfunction.


The clinical and radiological diagnosis of cartilaginous tumors of the base of the skull. Cartilaginous tumors of the base of the skull, though rare, comprise an interesting group of intracranial tumors which have rather distinct properties - somewhat characteristic clinical and radiologic signs, according to site of origin, and the potential for relatively long term survival even when malignant. It is the purpose of this paper to describe a clinical and radiologic experience with six such cases, a significantly useful series, as fewer than 150 cases have been reported in the world literature to date. This presentation comprises three segments. Initially, an introductory section outlines the basic historical, pathological, and radiological concepts. The second section comprises a clinical review of the case material and an analysis of the diagnostic and therapeutic characteristics. Finally, a section reviews the roentgen signs, including the role of specialized radiologic techniques to determine the specificity of x-ray findings.


The influx of uric acid and other purines into everted jejunal sacs of the rat and hamster. The in vitro transport of [2-14-C]uric acid, [8-14-C]hypoxanthine, and [8-14-C]xanthine, each dissolved in Krebs--Ringer bicarbonate buffer, was studied with everted jejunal sacs from rat and hamster. No evidence could be obtained for the development of a concentration gradient between the intracellular fluid and the incubation medium or between the sac contents and the incubation medium, for any of the three oxypurines. Inhibitiors of active transport, such as anaerobiosis for dinitrophenol, had no significant effect on the rate of transport. A large percentage of hypoxanthine and xanthine was oxidized to urine acid in the sac-wall homogenate, sac contents, and incubation medium during the course of the incubation. This oxidation could be prevented by addition of allopurinol (3 mM) to the incubation medium, but concentration gradients were still not obtained. No active transport mechanism could be demonstrated for uric acid, hypoxanthine, or xanthine in rat or hamster jejunum.


Extrahpetic distribution of sulfobromophthalein. Plasma clearance of sulfobromophthalein (BSP) is widely used as a measure of hepatic function. Its validity depends upon its exclusive elimination from the body via bile. For example, in the present study, when BSP was administered intravenously (i.v.) to rats at four different doses (18.75, 37.5, 75, and 150 mg/kg), less than 0.5% of each dose was excreted into the urine and between 70 and 85% was excreted into the bile within 6 h after administration. It has been assumed that the distribution of BSP is limited to the blood and liver witith very little appearing in other tissues. When we measured the amount of BSP in the plasma, liver, and the bile 10 min after the i.v. administration of either a high (150 mg/kg) or a low (18.75 mg/kg) dose of BSP, only 60% of the dose was accounted for. The concentration of BSP and 12-I-labelled albumin (RISA) was measured in various tissue samples 10 min after administration of 17.5 or 150 mg of BSP or RISA per kilogram. More BSP was found in all tissues than was contained in the plasma entrapped therein. Thus, the distribution of BSP is not limited to the liver and plasma. During excretion BSP leaves other tissue (kidney, spleen, lung, etc.) and is ultimately excreted into the bile.


Effects of adrenaline on the dynamics of carbohydrate metabolism in rats treated chronically with adrenaline. Following a subcutaneous injection of adrenaline (300 mug/kg), blood-glucose levels were lower in rats treated chronically with adrenaline (300 mug/kg twice a day for 28 days) than in control rats during at least 2.5 h after the injection. To explain this difference of response, the turnover rate of glucose was measured in control and adrenaline-treated rats during adrenaline infusion (0.75 mug/kg- minus 1 min- minus 1), with [U- minus 14C]glucose as tracer. It was found that the rate of appearance of glucose was greater in the control than in the adrenaline-treated group after a 120-min infusion of adrenaline. The rate of disappearance of glucose in the treated rats increased during the first 60 min of infusion and stayed at this elevated level for a subsequent 2 h, whereas in the control rats, it remained unchanged at the beginning of adrenaline infusion and significantly increased only during the second and third hours of infusion. In addition, the metabolic- clearance rate of glucose was not modified by adrenaline in the treated group, but in the control group, the initial clearance rate was significantly less than in the treated group, and decreased during the first hour of adrenaline infusion even though blood glucose reached values of 244 mg/100 ml. ,rom these data, it is suggested that rats adapt to a chronic exogenous supply of adrenaline by a reduced increase in glucose production in response to adrenaline infusion and a better glucose utilization, which possibly indicates a decrease in the inhibitory effect of adrenaline on insulin secretion.


Effective vascular compliance of dogs in acute heart failure. Effective vascular compliance was measured repeatedly in dogs without circulatory arrest utilizing a closed-circuit venous bypass system and constant cardiac output. Compliance, determined by the delta V/delta P relationship at the end of a 1-min infusion of 5% of the circulating volume into the inferior vena cava, was independent of the initial venous pressure, total circulating volume and systemic arterial pressure. It remained constant over a 3 h experimental period at 1.55 plus or minus 0.05 ml (mm Hg)-1-kb-1 body weight. Elevation of mean left atrial pressure and mean pulmonary arterial pressure by gradual aortic constriction was associated with a large and significant reduction in vascular compliance to a value of 1.14 plus or minus 0.06 ml (mm Hg)-1-kg-1 after 2 h. This reduction was independent of the initial venous pressure and total circulating volume but was associated with the changes in left atrial and pulmonary artery pressures and an increase in plasma catecholamine concentrations. The mechanism responsible for the reduction in effective compliance is not clear from the present experiments. Increased circulating catecholamines and sympathetic nerve traffic resulting from baro- and volume receptor stimulation in the vascular tree may be the causative mechanism.


Intestinal calcium-binding protein in animals fed normal and rachitogenic diets: I. Rat studies. Measurements were made of duodenal calcium-binding protein (CaBP) on rats during development of rickets and, subsequently, following vitamin-D2 treatment. Results showed a poor inverse correlation between duodenal CaBP and rickets. In rats fed a phosphate-deficient rachitogenic diet, duodenal CaBP concentration finally fell below detectable limits, but CaBP was still readily measurable 2 weeks after rickets was clearly established. Following a massive dose of vitamin D2 (50 000 I.U.) to rachitic animals, CaBP was formed. However, a small dose of vitamin D2 (500 I.U. daily for 4 days) was insufficient to demonstrate CaBP synthesis than vitamin-D treatment alone. The rachitogenic diet supplemented with phosphate, which caused osteoporosis but not rickets, inhibited CaBP synthesis. The results suggest that nutritional deficiencies from the rachitogenic diet, in addition to vitamin-D deficiency, inhibited CaBP synthesis.


Intestinal calcium-binding protein in animals fed normal and rachitogenic diets: II. Pig studies. Experiments were carried out in pigs to investigate the relationship between concentration of intestinal calcium-binding protein (CaBP) and the presence of rickets. Pigs made rachitic by a diet deficient in calcium and in vitamin D had concentrations of intestinal CaBP no less than values obtained on control pigs. These experiments, together with earlier work on rats (Can. J. Physiol. Pharmacol. 1975. 53, 137--143), demonstrate a poor inverse correlation between levels of intestinal CaBP and rickets.


Catecholamine-ouabain interaction on the isolated perfused rat heart. The effect of catecholamine-depleting pretreatments, reserpine, and 6-hydroxydopamine (6-OH-DA) on left ventricular pressure (LVP) and the inotropic response to graded doses of ouabain (up to 300 mug/0.05 ml) was studied in isolated perfused rat and guinea-pig hearts. In rats, reserpine and 6-OH-DA depleted the cardiac content of catecholamine, but did not increase initial LVP and did not reduce the inotropic response to the highest dose of ouabain. It is concluded that in isolated rat hearts, these catecholamine-depleting pretreatments nearly abolish the inotropic response to ouabain, and this effect appears to be mediated mainly through an increase in initial LVP. The reason why catecholamine depletion failed to increase initial LVP in guinea pigs remains unexplained.


A prolonged after-effect of intense synaptic activity on acetylcholine in a sympathetic ganglion. The findings was confirmed that there is a "rebound" increase of stored acetylcholine (ACh) in cat superior cervical ganglia conditioned by prolonged preganglionic stimulation at a frequency high enough to cause initial depletion of the store. Ganglia removed immediately after 60 min of continuous or interrupted stimulation at 50 Hz, with chloralose as anesthetic, contained about 30% more ACh than their unconditioned controls; the rebound rose to about 60% after 15 min of rest and then subsided with an apparent half-time of about 2 h. Tests with hemicholinium, combined with hexamethonium or tubocurarine, showed that rebound ACh was located presynaptically and could be released by nerve impulses; but conditioned ganglia perfused with an eserine-containing medium did not release more ACh than their unconditioned controls, except in circumstances in which the mobilization of ACh from a reserve store appeared to be the rate-limiting process for release. The appearance of rebound ACh during and after conditioning stimulation was suppressed by hexamethonium and by tubocurarine, neither of which has much effect on ACh turnover in ganglia excited at lower frequencies, but not only by atropine, noradrenaline, or phenoxybenzamine. The formation of rebound ACH is thus contingent on the postsynaptic nicotinic response to released ACh, and may represent an augmentation of the transmitter store in structures remote from the release sites.


Withdrawal rates of DDT from chickens treated with diphenylhydantoin. Male and female chickens of a broiler-type strain were fed, from 1 day old to 5 weeks of age, diets containing 0, 2.5, or 15.0 p.p.m. (mg/kg) 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT). Then the diets with pesticide were withdrawn and the chickens were fed dietary levels of diphenylhydantoin (DPH) at 0, 100, or 250 p.p.m. Adipose-tissue and liver samples were obtained on days 0, 10, 20, and 30 following withdrawal of diets with pesticides to determine DPH effect on DDT, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) levels. DPH had no effect on the concentration of DDT and DDE in adipose tissue; their levels declined at a rate having a half-life value of 16 days. DDD was not detected in adipose tissue. DDT accounted for 87% of the adipose residues on day 0, but 66% of the residues at day 30. DPH had no effect on the concentrations of DDT and DDE in livers of chickens fed 15.0 p.p.m. DDT, but did significantly reduce the levels of DDD by 28 and 54% for levels of 100 and 250 p.p.m. DPH, respectively. The similarity of these data to studies on dairy cows and humans, and the dissimilarity to data from rat studies were discussed.


Some pharmacological effects of prodolic acid, a new anti-inflammatory compound, indicative of inhibition of prostaglandin synthesis. Prodolic acid, a new non-steroidal anti-inflammatory compound, inhibited bradykinin-induced bronchoconstriction but did not affect histamine-induced bronchoconstriction in the guinea pig. Prodolic acid potentiated the responses of the isolated rabbit vas deferens and portal vein to electrical stimulation without altering the response to noradrenaline. The potentiating effects of prodolic acid on the vas deferens were reversible but the potentiating effects in the portal vein were frequency-dependent. It is concluded that these effects of prodolic acid are probably related to its ability to inhibit prostaglandin biosynthesis.


Thermal balance and survival time prediction of man in cold water. Metabolic rates and rectal temperatures were continuously monitored for humans immersed in cold ocean water (4.6--18.2 degrees C) under stimulated accident conditions. The subjects wore only light clothing and a kapok lifejacket while either holding-still or swimming. While holding-still, metabolic heat production (Hm,kcal-min--1) was inversely related to water temperature (Tw, degrees C) according to the equation Hm equals 4.19 minus-0.117 Tw. This temperature response pattern is shown to be similar to that for exposure to air of the same temperature when air velocity is just over 5 m.p.h. (2.24 m/s). The thermogenic response was one-third efficient in balancing the calculated heat loss in cold water, resulting in hypothermia at a rectal temperature cooling rate (C, degrees C-min--1) dependent on water temperature (Tw, degrees C) according to the relation C equal 0.0785 - 0.0034Tw. Although swimming increased heat production to 2.5 times that of holding-still at 10.5 degrees C water temperature, cooling rate was 35% greater while swimming. A prediction equation for survival time (ts, min) of persons accidentally immersed in cold water (Tw, degrees C) has the form ts equal 15 + 7.2/(0.0785-0.0034Tw), based on the findings of this study, and it is compared to pre-existing models.


Effects of short term ether and pentobarbital anesthesia on bone and cartilage metabolism. The effects of stress due to brief (4--5 min) ether and pentobarbital anesthesia vs. decapitation on assays of seven enzymes in homogenates of synovium, articular and epiphyseal cartilage, and metaphyseal and cortical bone were compared. Etherization caused twofold changes in synovial and articular cartilage G-6-PDH, LDH, CPK, glutamic DH, and ICDH based on tissue dry weight and DNA content. Pentobarbital anesthesia produced only slightly lower activities, per gram DNA, of LDH, acid phosphatase, and glutamic-DH in cortical bone. Epiphyseal cartilage metabolism was unaffected by either mode of anesthesia. No difference could be detected between levels of enzyme activities of the several tissues taken from rats that had been decapitated or anesthetized with pentobarbital. The changes in enzyme activities suggested that pentobarbital was non-stressful and appropriate to metabolic studies in the skeleton.


The effect of cocaine, reserpine, and 6-hydroxydopamine on the response of the perfused central artery of the rabbit ear to sympathomimetic amines. The perfused central artery of the rabbit ear was less sensitive to extraluminal than to intraluminal noradrenaline, but the reverse was true for metaraminol, methoxamine, metanephrine, and isoproterenol. No difference was noted between the extraluminal and intraluminal potency of phenylephrine. Cocaine potentiated the effect of extraluminal and intraluminal noradrenaline, but decreased that of intraluminal phenylephrine. Irrespective of the route of administration, the constrictor potencies of the sympathomimetic amines were not affected by cocaine. Arteries of reserpine-treated rabbits were supersensitive to extraluminally and intraluminally applied noradrenaline and phenylephrine, but they were not supersensitive to metaraminol. 6-Hydroxydopamine effectively destroyed adrenergic nerve endings of the central ear artery and increased its responses to both extraluminal and intraluminal noradrenaline and phenylephrine. However, only the constrictor potencies of intraluminally applied metaraminol and methoxamine were enhanced by 6-hydroxydopamine. The apparent discrepancies between the results obtained by various procedures that eliminate or impair the nerve uptake process suggest that the difference in the constrictor potency of extraluminal and intraluminal sympathomimetic amines is probably unrelated to their uptake by nerves located in the adventitio-medial junction of the artery.


Effects of modifiers on the optical properties of oxidized cholesterol model membranes. Brewster angle reflections from oxidized cholesterol membranes are described in terms of uniaxial crystal model. The refractive indices perpendicular and parallel to the membrane are 1.515 and 1.555, respectively. A multilayer model was also considered; however, under the approximations used, both models are equivalent and cannot be distinguished. Egg albumin and hexadecyltrimethylammonium bromide altered the refractive indices while 2,4-dinitrophenol and valinomycin addition did not produce a detectable change.


Molecular structure--activity relationship of hydrazides inhibiting glutamic acid decarboxylase, GABA-alpha-oxoglutarate aminotransferase, and monoamine oxidase activities in chick brain. Several aryl and heteroaryl hydrazides were synthesized and evaluated for their inhibitory effects on glutamic acid decarboxylase (GAD), GABA-alpha-oxoglutarate aminotransferase (GABA-T), and monoamine oxidase (MAO) enzyme systems in chick brain 24 h after their intramuscular administration (0.75 mmol/kg). All compounds produced a reduction in GAD, GABA-T, and MAO activity. Structure-activity relationships indicated that the ring structure had a greater influence on the degree of GAD and GABA-T inhibition than did the N'-terminal group. In contrast, structural requirements for MAO inhibition were much more restrictive. The intramuscular administration of benzoic acid hydrazide to chicks 24 h prior to their being exposed to oxygen at high pressure provided significant protection against the onset of the hyperbaric oxygen-induced seizures.


The effect of age on arterial--alveolar nitrogen difference in normal adults. The arterio--alveolar nitrogen difference (aADN2) has been associated in 27 normal adult subjects aged 20--60 years. As it may be assumed that venous and arterial PN2 are identical, we have used a sample of venous blood. There is a significant positive correlation between aADN2 and age. As the increase of aADN2 with age resembles that found in the literature for AaDO2, we concluded that the latter may be explained by increasing VA/Qc inequality within the lung.


The effect of insulin on glucose uptake in soleus muscle during hemorrhagic shock. Hemorrhagic shock was produced by bleeding conscious rats to a mean arterial pressure of 40 mm Hg, which was maintained for 2 h. Basal glucose uptake by isolated soleus muscle from normal rats and rats subjected to hemorrhagic shock ('shock' muscles) increased with the increase ib medium glucose concentration. Uptake values were similar in both groups of muscles. This indicates that there were no alterations in the basal glucose carrier mechanism during shock. Whereas insulin (0.1 U/ml) stimulated glucose uptake in control muscles under aerobic as well as under anaerobic conditions, it had no stimulatory effect in 'shock' muscles under either environment. Maximal stimulation of glucose uptake in 'shock' muscles was observed at an insulin concentration of 0.2 U/ml. The ability of muscle to bind insulin was not altered during shock. The present experiments indicate that insulin responsiveness to tissues is altered in shock. This could be due to alterations in the insulin sensitivity of the glucose carrier mechanism during shock.


The influence of prolonged hyper- and hypothyroid states on the noradrenaline content of rat tissues and on the accumulation and efflux rates of tritiated noradrenaline. The influence of chronic hyper- and hypothyroidism on the uptake and retention of tritiated noradrenaline ([3-H]NA) and on the endogenous noradrenaline (NA) content of various adrenergically innervated tissues was studied in thyroidectomized and sham-operated euthyroid rats. Half of the thyroidectomized rats were treated daily with thyroxine (25 mug/kg) for 3 or 12 weeks to simulate a condition of chronic hyperthyroidism, while the other half was left untreated to form a hypothyroid group. The body weight and the heart rate of each rat were measured at the end of each experiment, and in addition, at the end of the 3 week experiment, the oxygen consumption and the plasma thyroxine levels were measured to confirm the thyroid state of the animals. At the end of both experiments, each animal was given an intravenous injection of [3-H]NA and the [3-H]NA and the total endogenous NA content of the heart and various other adrenergically innervated tissues were measured on a timed schedule, to compare the initial accumulations and the rates of efflux of [3-H]NA under different thyroid states. Although the hyperthyroid rats had higher heart rates and heart weights, they were not significantly different from the euthyroid controls with respect to their body weights, tissue NA content, or accumulation and efflux rates of [3-H]NA. In contrast, the hypothyroid rats showed significantly lower heart and other tissue weights, but higher tissue concentrations of NA and rates of efflux of [3-H]NA than the euthyroid group. In the hypothyroid state, the NA turnover appeared to be increased as the [3-H]NA efflux rate was increased from the hearts and adrenal glands. There were no significant differences between the results of the 3 week and the 12 week experiments and no evidence that prolongation of the hyperthyroid state gave different results from those found by other workers who used much shorter treatment periods and larger doses of thyroxine to develop hyperthyroidism.


Effects of morphine and meperidine on action potential production in frog's skeletal muscle fibers. Morphine (3.3 times 10-minus 4 M) and meperidine (8.8 times 10-minus 5 M) inhibited action potential production in frog's skeletal muscle fibers. Over these concentration ranges, neither the resting membrane potentials nor the resting membrane electric properties of the fibers appeared to be modified. Both drugs depressed excitability and the rising phase of the action potential by inhibiting the specific increase in sodium conductance which normally follows an adequate stimulus. Both drugs also seemed to inhibit the secondary rise in potassium conductance which normally occurs during an action potential, causing a prolongation of the action potential duration.


Multiple hepatic excretory mechanisms for organic anions. A study with succinylsulfathiazole and taurocholate in the rat. A study was done to investigate interactions in the biliary excretion of [14-C]succinylsulfathiazole and [3-H]taurocholate after intravenous administration of the two compounds to anesthetized rats. Either compound administered alone increased bile flow and was excreted in the bile. The simultaneous infusion of both significantly increased bile flow above the values seen when either was given alone. However, the biliary-excretion rates of both compounds and their concentrations in bile were reduced when they were administered concomitantly. The simultaneous injection of radioactive taurocholate and succinylsulfathiazole did not alter significantly the plasma concentrations of either compound or their binding to plasma proteins from the values obtained when each was given alone. These results are consistent with a concept of competition between these compounds for the same liver-to-bile transport system. They contrast with previous observations that indicated that the concomitant administration of taurocholate increased the biliary excretion of acidic compounds. In the light of this work, it might be suggested that there are more than one transport system for the biliary excretion of organic anions.


The changing pattern of neoplastic disease in Canadian Eskimos. The records of the two main referral centres for the western and central Arctic were reviewed for Eskimo patients with cancer diagnosed between 1949 and 1974 inclusive. To these were added the records for the past 6 years of patients from the eastern Arctic, giving the toatal of 180 histologically proved cases of malignant disease. Athe data were analysed for prevalence, relative frequency, geographic distribution and changes with time of the various neoplasms. Salivary gland and renal neoplasms have in recent years been displaced by cancer of the lung and uterine cervix as the most common malignant tumours in Canadian Eskimos. The prevalence of lung cancer in Eskimo women, particularly of the central Artic, is striking. Cancer of the nasopharynx kept the same relative position during early and late years of the survey period. Breast cancer is still uncommon in Eskimos. Lactation rather than gestation history appeared to be an important protective factor. Cases of cervical cancer outnumbered those of breast cancer by 18 to 4, in sharp contrast to the relative proportions of these tumours in all Canadian women.


Multiple fluoroscopy of the chest: carcinogenicity for the female breast and implications for breast cancer screening programs. The risk of radiation carcinogenesis has been established for breast tissue from experience with total body irradiation and multiple fluoroscopy of the chest with the patient prone. The doubling dose has been estimated to lie between 20 and 50 rads. Before undertaking radiologic screening programs for breast cancer, therefore, it is necessary to determine whether exposures below this range are safe. Of 792 women who had had tuberculosis and were followed for a minimum of 20 years, 451 had had multiple fluoroscopy while supine; 341 had not had fluoroscopy. The first group received a total radiation dose to the breast averaging 17 rads (141.5 fluoroscopies); the incidence of breast cancer in this group was not increased. Had fluoroscopy been performed with the patient prone the total radiation dose would have averaged 308 rads. The difference is thought to explain the increased incidence of breast cancer attributable to fluoroscopy given with the patient prone. Mid-breast exposure with mammography or xeroradiography varies between 3 and 6 rads. Repetitive screening would, therefore, appear safe provided total exposure did not exceed 20 rads. With this restriction there would appear to be no reason to curtail screening of women for breast cancer.


Nurse practitioners in primary care iv. Impact of an interdisciplinary team on attitudes of a rural population. Attitudes toward the expanded role of nurse practitioners in primary care (family practice nurses) have been determined for persons from a semirural area who chose as their principal souce of care an interdisciplinary family medical centre (FMC) incorporating two nurse practitioners, and those for whom the FMC was not the usual source of care. Data were obtaine using"before-and-after" structured interviews of a random sample of persons living in a southern Ontario township. Slowly evolving, nonsignificant trends of greater acceptance were observed among patiens who had  dealth with family practice nurses. The greatest change observed was an increased acceptance of the nnurse by FMC users as the person who would be contacted as a second choice if theirfirst choice, usually a physician, could not be reached in specific worrry-inducing situations. FMC users depended more on nurses to provide information. A conclusion of increased general acceptance of the family practive nurse by FMC users is supported by a 34 per cent higher use of nurses by FMC patients compared to other persons of comparable characteristics living in the same community.


Gastritis cystica and carcinoma arising in old gastrojejunostomy stoma. Gastritis cystica and carcinoma developed 35 years after partial gastectomy and gastrojejunostomy for benign peptic ulcer. Although chronic atrophic gastritis and carcinoma are well recognized complications of gastrojejunostomy, gastritis cystica appears to be rare. The resemblance of the lesion to that of colitis cystica profunda is striking.


The role of surgery in the management of thyroid cancer. This is a review of one surgeon's personal experience with 85 patients with thyroid cancer treated over a 20-year period. The data confirm that for papillary thyroid tumours, with rare exceptions, the prognosis is excellent. Anaplastic lesions, however, are consistently lethal. Follicular carcinoma and medullary carcinoma fall between these extremes. A simple clinical classification is offered as a guide to operative management and a reliable index of prognosis. Patients with clinically apparent, "manifest cancer" have serious, life-threatening disease; many such patients die of their disease. Patients with "neck lumps not yet diagnosed" usually have papillary carcinoma; their prognosis is excellent. Patients whose thyroid tumours fall into the category of "malignant nodule" or "pathologist's cancer" are particularly fortunate: in this series no such patient has died. The importance of age in relation to thyroid cancer is also confirmed: non of the patients first treated before the age of 40 years has died of cancer. For young patients with favourable disease the author recommends conservative surgical treatment, which avoids cosmetic deformity or functional disability, to be followed by administration of levothyroxine to suppress production of thyroid=stimulating hormone. For patients with "unfavourable" thyroid cancer valuable palliation can often be achieved by a combination of surgery and irradiation. Survival rates for the total series are 76% at 5 years and 60% at 10 years.


Radiotherapy in thyroid cancer.

Radiotherapy in thyroid cancer. Although resection is the mainstay of treatment of thyroid cancer, and radioactive iodine (131-1) is curative in a small number of patients with differentiated cancers, external irradiation is much more effective than is generally believed. This has been clearly shown in a review of 138 patients with thyroid cancer referred to a cancer centre, in most cases after an initial operation. External irradiation should be considered in all patients except those with pure papillary tumours that have been completely excised. It should be used (a) in conjunction with surgery if there is even a remote doubt as to the completeness of excision; (b) in conjunction with 131-1 in treating inoperable primary tumours or metastatic lesions; () alone for differentiated tumours (primary or metastatic) that do not take up 131-1; and, (d) perhaps combined with chemotherapy, for medullary and anaplastic tumours.


Patient morbidity and some patterns of family practice in southeastern Ontario. Over a 7-month period the trial version of the International Classification of Health Problems in Primary Care (ICHPPC) was studied. Ten community physicians reported 28 399 encounters wtith 11 437 patients. The overall distribution of health problems was comparable to that found in other North American studies. Some differences between the morbidity distributions in urban and rural practices varies from those of previous Canadian studies. Other differences between practices appeared to be related to the interests and training of the individual physicians. The workload of the physicians varied considerably. Many of the encounters involved problems for which there may be minimal benefit from medical intervention, and there was a large discrepancy in the frequency of follow-up visits for specified stable chronic health problems. The implications of these interpractice variations in the altering field of health care are discussed.


Interpretation of the PPD skin test in BCG-vaccinated children. Skin testing with 5 tuberculin units (TU) of purified protein derivative (PPD) of tuberculin stabilized with polysorbate (Tween) 80 was done 3 months and 1 year after immunization with bacille Calmette-Guérin (BCG) vaccine in two groups of children: one group vaccinated at birth and another group at age 6 years. Interpretation of the PPD skin test with 5 TU is possible in children 1 year and older vaccinated with BCG at birth: if the diameter of induration is more than 10 to 12 mm the reaction cannot be ascribed to BCG vaccination and is highly suggestive of supervening infection with Mycobacterium tuberculosis or occasionally atypical mycobacteria. In contrast, the interpretation of a PPD test in children vaccinated at age 6 years is extremely difficult.


Fatal fat embolism during ritual initiation. A young Coast Salish Indian woman became fatally ill during ritual Initiation into the Native Winter Spirit Dancing Society. She died from massive fat emboli associated with subcutaneous bruises that appeared clinically unimportant and were not associated with fractures or other underlying injury. The liver showed extreme fatty metamorphosis.


Letter: Ischemic heart disease, water hardness and myocardial magnesium. In 54 cases of accidental death in cities with water hardness of 60 parts per million (ppm) or less, the mean myocardial magnesium concentration was 918 mug/g of dry tissue. This was 7% lower than the corresponding figure of 982 mug/g among 29 cases of accidental death in cities with water hardness of 300 ppm or more, and this difference was significant (P less than 0.01). There were no significant differences between the cities with soft and hard water in the mean myocardial concentrations of calcium, zinc, copper, chromium, lead or cadmium. These results are compatible with the belief that the relatively high death rates in some soft-water areas may be due to a suboptimal intake of magnesium, and that water-borne magnesium exerts a protective effect on the residents of hard-water areas.


Letter: The clinical course of patients with analgesic nephropathy. Thirty-four patients with analgesic nephropathy were followed at intervals of 1 to 3 months with measurements of creatinine clearance and serum concentration of acetylsalicylic acid (ASA) for a total of 105 patient-years. Diagnostic criteria included total consumption of at least 2 kg of phenacetin and 3 kg of ASA, compatible tissue abnormality on biopsy and evidence of papillary necrosis on an intravenous pyelogram. Nephropathy was induced by the same compound analgesic containing ASA, pehnacetin, caffeine and codeine (APC&C) in 30. Phenacetin was removed from this preparation in 1970 and replaced by an approximately equal amount of ASA (ACC). Creatinine clearance remained unchanged or improved in 11 of 15 patients who stopped taking analgesics containing phenacetin or ASA and in 10 of 11 of those who continued to take the ACC preparation. In contrast, renal function deteriorated in seven of eight patients who continued to abuse APC&C analgesics. The results suggest that phenacetin is necessary for the major nephrotoxic effect of this APC&C combination, but that ASA is not absolved of some nephrotoxicity.


Dyspareunia: a symptom of female sexual dysfunction. Dyspareunia is one of the most common sexual symptoms that carries wide-ranging potential foor emotional and physical pain. Informed therapeutic intervention can be useful in helping a person with sexual problems. Organic causes underlying dyspareunia are usually temporary and easily correctable. They are rare as a cause of a continuing problem, compared to issues of intrapersonal and interpersonal conflict. One of the keys to achieving a satisfying relationship on an adult-to-adult basis requires that each partner assume responsibility for his/her own sexual pleasure. The woman who withdraws into the assumption that she has an organic problem in the absence of abnormal findings, or that her partner or therapist must find a solution, abdicates responsibility for her own sexual pleasure. Although few of us will be therapists in the sense that the role is generally understood, indentifying and responding to sexual concerns of patients is part of the professional's commitment. Ultimately, our goal is the same for any problem of human development-- to facilitate the realization of the potentialities of the person.


Determination of position of substitution on 2-acetamido-2-deoxy-D-galactosyl residues in glycolipids. The substitution site on 2-acetamido-2-deoxy-D-galactosyl residues in oligosaccharide chains of glycolipids was determined by permethylation of the glycolipid with methyl iodide in the presence of dimethylsulfinyl carbanion, methanolysis of the permethylated product under mild conditions, acetylation with acetic anhydride-pyridine, and identification of the resulting substituted methyl glycosides of 2-deoxy-2(N-methylacetamido)-D-galactose by g.l.c. The method was applied to glycolipids of known structure, including normal brain ganglioside, Tay-Sachs ganglioside, and Forssman glycolipid.


Nucleosides LXXXIX. Synthesis of 1-(2-chloro-2-deoxy-alpha- and -beta-D-arabinofuranosyl)cytosines. 1-(2-Chloro-2-deoxy-beta-D-arabinofuranosyl)cytosine (16) and its alpha anomer (18) were synthesized by direct condensation of 3,5-di-O-acetyl-2-chloro-2-deoxy-alpha-D-arabinofuranosyl bromide with trimethylsilylated N-4-acetylcytosine in the absence of catalyst. A new and convenient method for the synthesis of 1,3,5-tri-O-acetyl-2-chloro-2-deoxy-alpha-D-arabinofuranose from methyl 3,5-di-O-benzyl-alpha,beta-D-ribofuranoside is described.


Synthesis of DL- and D-gluco-hept-3-ulose. DL-gluco-Hept-3-ulose was synthesised by oxidation of tri-O-isopropylidene-meso-glycero-gulo-heptitol with methyl sulphoxide-phosphorus pentaoxide, and subsequent hydrolysis. D-gluco-Hept-3-ulose (3) was synthesised by oxidation of one of the two isopropylidene derivatives from perseitol (D-glycero-D-galacto-heptitol), which is presumed to have the 2,2:4,5:6,7 structure, followed by hydrolysis. The crude product from the reduction of DL-gluco-hept-3-ulose with sodium borohydride showed two peaks corresponding to meso-glycero-gulo-heptitol and perseitol on g.l.c. of the trimethylsilyl derivatives. Isolation and acetylation of the latter heptitol revealed it to be racemic perseitol. Oxodation of DL-gluco-hept-3-ulose with oxygen in alkali followed by treatment with ferric acetate-hydrogen peroxide gave products with chromatographic behaviour characteristic of arabinonolactone and erythrose. Treatment of DL-gluco-hept-3-ulose with 2,4-dinitrophenylhydrazine gave a 1-deoxy-2,4-dinitrophenylosazone.


Gamma-radiolysis of D-glucose in aerated, aqueous solution. Gamma-Radiolysis of D-glucose in aerated, aqueous solution gives mainly D-glucono-1,5-lactone, D-arabino-hexosulose, and D-ribo-hexos-3-ulose, together with D-xylo-hexos-4-ulose, D-xylo-hexos-5-ulose, and other pentose, tetrose, and triose derivatives as minor products, which were estimated by mass spectrometry of their alditol-d acetates. These hexose derivatives appear to be produced by the decomposition of D-glucose peroxy-radicals which are formed by the reaction of the primary radicals of D-glucose with oxygen. Bond scission of the peroxy-radicals yields triose, tetrose, and pentose. A radiolysis mechanism for the degradation of D-glucose in aerated, aqueous solution is proposed, based on the reaction of several kinds of D-glucose radical with oxygen.


The action pattern of Penicillium lilacinum dextranase. The product distributions resulting from the action of Penicillium lilacinum dextranase on end-labelled oligosaccharides of the isomaltose series have been determined. The initial rates of formation of labelled products were measured for isomaltotriose up to isomalto-octaose, and the molar proportions and radioactivity of the final products from isomaltotriose up to isomaltohexaose were determined. D-Glucose was released only from isomaltotriose and isomaltotetraose, by hydrolysis of the first linkage from the reducing end (linkage 1); the terminal bonds of higher members of the series were not attacked. All oligosaccharides except isomaltotriose were hydrolyzed at more than one linkage. The main points of attack on isomaltotetraose up to isomalto-octaose were at linkage 2, and at the third linkage from the non-reducing end; these two positions coincide for isomaltopentaose. The degradation of isomaltotriose up to isomalto-octaose was entirely hydrolytic. The enzyme also catalyzed an extremely slow, concentration-dependent degradation of isomaltose, and this may have occurred via a condensation to isomaltotetraose, followed by hydrolysis of linkage 1 to give D-glucose and isomaltotriose.


Presence of soluble lignin-carbohydrate complexes in the bovine rumen. The cell-free rumen liquor of a steer on a diet of spear grass has been shown to contain macromolecular substances in which carbohydrates and lignin-derived compounds are covalently bound to each other. The lignin-carbohydrate complexes are soluble at pH 7 or higher, but precipitate at pH 3. At the latter pH, small amounts of a polymer, assumed to be glycoprotein, remain in solution. Some of the lignin-carbohydrate linkages are broken by treatment with alkali. Treatment with 50mM sulphuric acid for a few minutes at room temperature converts part of the complex into an acetone-soluble product, which still contains both carbohydrate and lignin-derived compounds. The formation of soluble lignin-carbohydrate complexes by the action of rumen micro-organisms on the grass may account for the dissolution (and hence the apparent digestion) of about half of the total lignin-intake.


The quantitative analysis of uronic acid polymers by infrared spectroscopy. I.r. absorption bands associated with the functional groups of carboxylic acid derivatives are useful for the analysis of alginates and pectins. The ester, amide, and uronate contents of pectins and the uronate content of alginates were determined, respectively, from the ester-carbonyl stretching band (1740 cm- minus 1), the amide I band (1650 cm- minus 1), and the carboxylate antisymmetric stretching band (1607 cm- minus 1) obtained from the spectra of solutions in D2O-phosphate buffer. The results are accurate to within plus or minus 2-4%, are self consistent, and agree well with the few reliable results that are available. The method should be applicable for the determination of carboxylic acid derivatives in other polysaccharides.


A practical synthesis of 2-deoxy-2-fluoro-D-arabinofuranose derivatives. A seven-step synthesis of 1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose, a versatile intermediate in the synthesis of chemotherapeutically important nucleosides, was achieved from 1,2:5,6-di-O-isopropylidene-3-O-tosyl-alpha-D-allofuranose. The crucial steps were the fluorination by use of potassium fluoride in acetamide and the conversion of 6-O-benzoyl-3-deoxy-3-fluoro-D-glucofuranose into 5-O-benzoyl-2-deoxy-2-fluoro-3-O-formyl-D-arabinofuranose by periodate oxidation. Also described is the synthesis of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosine. This procedure affords good overall yields of products without formation of undesirable, isomeric intermediates and is suitable for large-scale preparations.


[Synthesis of 2-acetamido-2-deoxy-4-O-alpha-L-fucopyranosyl-alpha-D-glucopyranose]. Condensation of 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide with benzyl 2-acetamido-3,6-di-O-benzyl-alpha-D-glucopyranoside in dichloromethane-N,N-dimethylformamide, in the presence of tetraethylammonium bromide, diisopropylethylamine, and molecular sieve (halide ion-catalyzed reaction), gave benzyl 2-acetamido-3,6-di-O-benzyl-2 deoxy-4-O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-alpha-D-glucopyranoside in crystalline form in 82% yield. Hydrogenolysis of the benzyl groups gave the title disaccharide, in crystalline form in 90% yield, which was characterized by a crystalline peracetylated alpha-D derivative.


Synthesis and spectral properties of cytosine nucleosides of 2-amino-2-deoxy-alpha-D-arabino-furanose and -pyranose. Ethyl 2-deoxy-3,5-di-O-p-nitrobenzoyl-1-thio-2-(trifluoroacetamido)-beta-D-arabinofuranoside (3) was converted into the glycosyl chloride. Condensation of the latter with 2,4-dimethoxypyrimidine, followed by amination, gave 1-(2-amino-2-deoxy-alpha-D-arabinofuranosyl)cytosine (6), which was also obtained from the alpha-D anomer (4) of 3. Similarly, 1-(2-amino-2-deoxy-alpha-D-arabinopyranosyl)cytosine (12) was synthesized from ethyl 2-deoxy-3,4-di-O-p-nitrobenzoyl-1-thio-2-(trifluoroacetamido)-alpha-D-arabinopyranoside (9). The p.m.r. spectra of these nucleosides, as well as those of the 1-thioglycosides, are discussed in terms of the conformation of the sugar portion. In particular, a large change of the J1,2 coupling constants of the alpha-D-furanosides, according to the substituents at C-1 and C-2, was interpreted on the basis of conformational mobility.


Synthesis of a cytosine nucleoside of 2-amino-2-deoxy-beta-D-xylofuranose. 1-(2-Amino-2-deoxy-beta-D-xylofuranosyl)cytosine (13) was synthesized by three routes: (a) coupling of 2-deoxy-3,5-di-O-p-nitrobenzoyl-2-(trifluoroacetamido)-D-xylofuranosyl chloride (5) with 2,4-dimethoxypyrimidine and subsequent treatment with methanolic ammonia, (b) coupling of 5 with 4-N-acetyl-2-O,4-N-bis(trimethylsilyl)cytosine followed by treatment with methanolic ammonia, and (c) thiation of 1-[3,5-di-O-acetyl-2-deoxy-2-(trifluoroacetamido)-beta-D-xylofuranosyl]uracil (6) by treatment with phosphorus pentasulfide in pyridine followed by amination of the resulting 4-thionucleoside 12 with metanolic ammonia. The best yield was obtained via route (a).


Structural characteristics of native and enzymically formed dextran of S. sanguis ATCC 10558. The structure of the native dextran produced by Streptococcus sanguis ATCC 10558 was analyzed by g.l.c.-m.s. of the methylated alditol acetates derived from the polymer. The results indicate that the polymer contains D-glucosyl residues substituted at C-6 or C-3, or both, as well as unsubstituted D-glucosyl residues. These data aially purified dextransucrase on sucrose. The proportion of D-glucosyl residues substituted at C-3 is diminished in this case. It is concluded that several enzymes are involved in the dextran synthesis.


Determination of the time course of left ventricular wall stress and velocity of fiber shortening in man by simultaneous left ventricular pressure and echocardiographic recording: preliminary report. This report presents a method for determining the time course of circumferential LV wall stress and fiber shortening velocity (endocardial as well as midwall) using simultaneous recordings of LV dimensions by echography and LV pressure (micromanometer). The values for max VCF, VCF at peak stress, mean VCF, and peak stress are in general agreement with those observed with previous methods; the separation between normal and abnormal LV function appears to be good. The method permits frequent observations to be performed in a single patient, which is of particular value during acute interventions. Data from a small number of interventions suggest that VCF in man is relatively insensitive to acute changes in preload, is inversely affected by changes in afterload and appears sensitive to inotropic stimulation. Although VCF seems to be a good index of LV performance, its sensitivity to afterload might, at times, limit its usefulness.


Compartments and cell flows within the mouse haemopoietic system. I. Restricted interchange between haemopoietic sites. Two chromosomally distinguishable haemopoietic cell populations were injected into lethally irradiated syngeneic recipients. The presence or absence of the T(14;15)6Ca reciprocal translocation (indicated by T6 marker chromosomes) did not affect the proliferation of a population. Wide disparities were found in the proportions of the two donor cell populations between animals and between the right and left femora of individual animals. This suggest (i) that there is, at most, a very limited interchange of proliferating cells and their precursors between the marrow of different bones; and (ii) that the number of clones proliferating in the bone marrow at any one time must be rather small; there was evidence that this number depended in part on the number of haemopoietic cells injected. Exchange between the mitotically active cell populations of spleen, thymus, lymph nodes and bone marrow was also limited, as shown by significant disparities in the proportions of the two donor populations proliferating in the different tissues of individual mice.


The effect of estradiol on the cell kinetics in the uterine and cervical epithelium of neonatal mice. The effect of estradiol-17beta on the length of the various phases of the cell cycle was studied in the neonatal mouse uterine, and cervical epithelium. A double labelling method was used, and in addition labelled mitoses were counted. In the uterus proper, estradiol shortens the length of the total cell cycle. TC, from 17-9 hr to 15-7 hr, and the duration of S phase, Ts from 6-7 to 5-1 hr 6 hr after estradiol treatment. 12 hr after estradiol treatment, TC is shortened to 7-4 hr and Ts to 4-5 hr. The shortening of TC at 12 hr is manily due to an effect on TG1, which is shortened from 8-55 hr in untreated animals to 1-8 hr in estradiol treated animals. The TC of cervix epithelium cells in untreated animals was found to be 21-8 hr. After treating the mice for 6 hr with estradiol the tc was now increased to 47 hr and further to 61-2 hr following 12 hr treatment with the hormone. Ts increases from 8-3 hr to 15-2 hr following 6 hr estradiol treatment, and to 15-4 hr after 12 hr treatment. The effect is most pronounced in TG1, which is lengthened from 10-95 hr in untreated animals to 28-1 hr and 43 hr, respectively, in animals treated for either 6 or 12 hr with estradiol.


An autoradiographic and morphological study of mouse bone marrow littoral cells during and after treatment with urethane. This study demonstrates that the labeling index of mouse marrow littoral cells can be markedly altered as a result of treatment with ethyl carbamate (urethane). Young C57/BL mice were given daily intraperitoneal urethane injections for periods up to 6 days. Following treatment each day, as well as daily over a 10 day recovery period, a group of animals was administered tritiated thymidine every 3 hr over a 24 hr period and sacrificed 1/2 hr after the last injection. Marrow was embedded in epon and 0-5 mum sections cut for autoradiographic and light microscopic analysis. A thirty-five-fold increase in the percentage labeled littoral cells was observed after three injections of urethane. The labeling index of littoral cells fluctuated during the treatment period and during the 10 day recovery period. The albeling data are discussed in relation to the possible effects of urethane on the cell cycle of mouse marrow littoral cells; the morphological sequela to urethane treatment and the possibility that littoral cells may act as stem cells.


Reprogramming in the absence of DNA synthesis in Galleria larval epidermis. Larval epidermal cells from a day-1 penultimate instar Galleria larva on implantation into day-5 last instar larva metamorphose and deposit a pupal cuticle at the same time as the host pupates. DNA synthesis in the implanted larval cell was monitored with 3-H-thymidine. Various regimens of 3-H-thymidine application were used and under no conditions did the larval cells incorporate label during the period from implantation to deposition of pupal cuticle. This suggests that a wax moth larval ectoderm cell can reprogram its genome to secrete a pupal cuticle without a precedent cell division.


The effect of 5-bromodeoxyuridine on the synthesis of nuclear and cytoplasmic DNA-binding proteins isolated from sea urchin embryos. Newly synthesized DNA-binding proteins were isolated from the nuclei and, separately from, the cytoplasm of sea urchin mofula stage embryos. The presence of 5-bromodeoxyuridine during embryogenesis did not appear to alter the synthesis of either class of DNA-binding proteins. This result tends to argue that cell differentiation in early embryos is not regulated by differential synthesis of DNA-binding proteins. Sea urchin mofulae synthesize a broad range, by molecular weight, or cytoplasmic DNA-binding proteins which dissociate from sea urchin DNA-cellulose at relatively high salt concentrations (0.6-2.0 M NaCl). The most prominant of these apparently high-binding-affinity proteins has an approximate molecular weight of 33,000.


The action of arachidonic acid on the locomotive activity of mice. The intraperitoneal administration of methyl or sodium arachidonate (100 and 200 mg-kg causes, in mice, a significant decline in locomotive activity 30 min later, and is able to oppose completely the antagonistic action of D-amphetamine (2.5 and 5 mg-kg). This effect seems to be related to increased synthesis of prostaglandins, for it disappears partially after pretreatment with acetylsalicylic acid, which alone has no effect on the spontaneous activity of mice. Oleic acid, an unsaturated fatty acid not involved in prostaglandin synthesis does not give significant results in the same conditions.


Characterization of monosomes produced by aflatoxin B1. A single injection of 1.5 mg aflatoxin B1 per kg body weight produced approx. 70% disaggregation of rat liver polysomes into monosomes within 18 h. Isolated monosomes dissociated into 40 S subunits during centrifugation in linear sucrose gradients containing 0.3 M KCI. The 4 S to 5 S molar RNA ratio of the monosomes was calculated to be 0.6, indicating 0.6 tRNA and/or aminoacyl tRNA molecule per ribosome; no peptidyl tRNA was present. These results suggest that a single injection of affatoxin B1 produces monosomes which resemble runoff ribosomes.


Effects of phenobarbital on protein synthesis and polysome levels in rat liver. Administration of phenobarbital to rats increases the rate of synthesis of certain microsomal drug-metabolizing enzymes in a selective manner and promotes proliferation of smooth endoplasmic reticulum in the liver. Phenobarbital increased a number of factors by which protein synthesis could be enhanced in the liver. It produced a 30% increase in the amount of ribosomes and mRNA per cell. The proportion of ribosomes associated with polysomes was increased by 5-10% over normal liver. There was a 10-30% increase in the rate of ploypeptide elongation and a small increase or no change in polysome size, indicating that the rate of polypeptide initiation was increased proportionately. The product of these effects accounts for the 1.5-fold increase in the rate of total protein synthesis previously reported. The average polysome size, and the size of free polysomes in particular, was maintained when actinomycin D was administered to phenobarbital-pretreated rats, suggesting that the rate of mRNA degradation was decreased selectively. Phenobarbital did not, however, affect the distribution of ribosomes between the free and membrane-bound states or the activity of ribonucleases associated with isolated free and bound polysomes. Thus, we conclude that phenobarbital stimulates protein synthesis by expanding the mRNA pool, at least partially through effects on mRNA degradation, and by augmenting the rate of mRNA translation.